探討血清素2B接受器對蝕骨細胞生成作用的影響

Study the Role of Serotonin 2B Receptor (5-HT2BR) in Osteoclastogenesis

林萱雅(Shiuan-Yea Lin)

指導教授 ： 鄭琮霖

高雄醫學大學/醫學院/醫學系生理學科碩士班/碩士(2015年)

https://doi.org/10.6832/KMU.2015.00055

摘要

骨質疏鬆症（Osteoporosis）是罹患率僅次於心血管病變的疾病，也是中老年人及停經後婦女常見的疾病之一。造成骨質疏鬆的主要原因之一是體內蝕骨細胞生成作用（Osteoclastogenesis）過高，因而導致骨質流失。蝕骨細胞是由單核球/巨噬細胞融合、分化而成。近年臨床研究發現，長期服用選擇性血清素回收抑制劑（Selective Serotonin Reuptake Inhibitor, SSRI） 類抗憂鬱症藥物之患者，其罹患骨質疏鬆症的比例明顯偏高，暗示血清素 （Serotonin, 5-HT）很可能參與骨質代謝的調控。過去報導指出，成骨細胞及蝕骨細胞上都會表現血清素2B型接收器（Serotonin 2B Receptor, 5-HT2BR），且5-HT2BR的活化有促進成骨細胞增生及分化的功能，但對於蝕骨細胞的影響則尚未有明確答案。此外，最近的研究顯示，細胞內的Silent Information Regulator T1（SirT1）可透過調節核因子-B（NF-B）活性，進而調控蝕骨細胞的生成與分化。本研究利用核因子κ-B配體受體致活劑 （RANKL）誘導RAW264.7細胞分化蝕骨細胞為模式，探討5-HT2BR在蝕骨細胞分化過程中所扮演的角色。結果顯示，蝕骨細胞分化程度與5-HT濃度成正相關，如果給予5-HT2BR興奮劑亦可促進蝕骨細胞分化，並且明顯降低細胞中SirT1表現量。反之，給予5-HT2BR的拮抗劑處理，亦能顯著性抑制與降低蝕骨細胞的形成。再者，給予SirT1 興奮劑確實可抑制蝕骨細胞的生成。簡言之，本研究證實 5-HT2BR確實參與調控蝕骨細胞生成作用，而其中分子機制確實與SirT1有關。本研究成果或許可為骨質疏鬆症的預防與治療提供一個新方向。

關鍵字

蝕骨細胞 ； 血清素 ； 骨質疏鬆症

並列摘要

Osteoporosis is the common diseases in menopausal women and elderly people, and its incidence just lower than cardiovascular disease. Excessive osteoclastogenesis is one of the main reasons to cause osteoporosis. Recent clinical researches indicated that the patients’ long-term use of anti-depression drugs (Selective Serotonin Reuptake Inhibitor, SSRI) usually with higher risk to suffer osteoporosis. This observation means serotonin, 5-HT, should involve in the regulation of bone metabolism. Previous reports showed that 5-HT 2B receptor (5-HT2BR) is expressed in both osteoblasts and osteoclasts, and which modulate the proliferation and differentiation in osteoblasts. However, the effects of 5-HT2BR in osteoclasts remain unclear. Using RANKL-induced osteoclastogenesis in RAW 264.7 cells as the model, our results presented a positive correlation between the osteoclastogenesis with 5-HT and 5-HT2BR agonist treatment and that decrease SirT1 expression. On the contrary, treatment with specific 5-HT2BR antagonist significantly reduced the osteoclastogenesis and increase SirT1 expression. Treatment with SirT1 agonist significantly reduced the osteoclastogenesis. Taken together, this investigation suggested that 5-HT2BR play an essential role in osteoclastogenesis and may be involved in regulating osteoporosis. Our observations might also provide another direction of prophylaxis and therapy for osteoporosis.

並列關鍵字

osteoclast ； serotonin ； osteoporosis

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